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AHR and tryptophan metabolism: a collaborative dynamics of immune regulation

Genes & Immunity volume 25, pages 170–171 (2024)Cite this article

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A profound comprehension of the intricate regulatory mechanisms within the immune system is essential for navigating the complexities of cancer and immunotherapy. This commentary paper delves into the intricate interplay between tryptophan metabolism, the enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan-dioxygenase (TDO), and the aryl hydrocarbon receptor (AHR). These elements play pivotal roles in shaping immune responses, particularly in advanced-stage cancers, where their overexpression is associated with poor prognosis and immune suppression [1].

Studies examining the effects of immune suppression caused by IDO and TDO tended to focus separately on the outcomes of tryptophan deprivation and kynurenine production. The connection between IDO and AHR has long been associated with the metabolite kynurenine [2]. Recent research by Solvay et al. has revealed the complex ways in which AHR activation is influenced by both the lack of tryptophan and the production of kynurenine [3]. This interaction demonstrates the impressive complexity of the immune suppression orchestrated by the enzymes IDO and TDO. Specifically, it has been found that when tryptophan is in short supply, it can boost the expression of AHR and make it more responsive to ligands, especially making it more sensitive to relatively weak triggers like kynurenine. Importantly, this increased sensitivity has been demonstrated to favor the in vitro differentiation of regulatory T cells (Tregs).

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Fig. 1: IDO/TDO-Enhanced AHR Activation.

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Authors and Affiliations

  1. de Duve Institute, UCLouvain, Brussels, B-1200, Belgium

    Jingjing Zhu & Benoit J. Van den Eynde

  2. Ludwig Institute for Cancer Research, Brussels, B-1200, Belgium

    Jingjing Zhu & Benoit J. Van den Eynde

  3. WEL Research Institute, Brussels, B-1200, Belgium

    Jingjing Zhu & Benoit J. Van den Eynde

  4. Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

    Benoit J. Van den Eynde

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  1. Jingjing Zhu
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  2. Benoit J. Van den Eynde
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JZ originated and composed the manuscript, and BJVdE provided revisions and valuable comments.

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Correspondence to Jingjing Zhu.

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The authors declare no competing interests.

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Zhu, J., J. Van den Eynde, B. AHR and tryptophan metabolism: a collaborative dynamics of immune regulation. Genes Immun 25, 170–171 (2024). https://doi.org/10.1038/s41435-023-00235-6

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  • DOI: https://doi.org/10.1038/s41435-023-00235-6

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